combined oxidative phosphorylation deficiency 7

Combined oxidative phosphorylation deficiency 7 (COXPD7) is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis. This condition is characterized by a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations such as ptosis, nystagmus, optic atrophy, ophthalmoplegia, and other symptoms.

The disease is caused by a homozygous mutation in the C12ORF65 gene, which encodes a mitochondrial matrix protein critical for mitochondrial metabolism. This defect leads to impaired oxidative phosphorylation, resulting in encephalomyopathy, psychomotor delay and regression, ataxia, optic atrophy, and other systemic manifestations.

COXPD7 is an autosomal recessive disorder, meaning that it is inherited in an autosomal recessive pattern. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

The symptoms of COXPD7 can vary widely among affected individuals and may include:

• Failure to thrive and psychomotor regression
• Ocular manifestations such as ptosis, nystagmus, optic atrophy, ophthalmoplegia
• Encephalomyopathy
• Ataxia
• Other systemic manifestations

Early diagnosis and management of COXPD7 are crucial for improving outcomes and quality of life for affected individuals.

References:

[1] Combined oxidative phosphorylation defect type 7 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations (such as ptosis, nystagmus, optic atrophy ... [2] [3] Combined oxidative phosphorylation defect type 7 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations (such as ptosis, nystagmus, optic atrophy, ophthalmoplegia ... [4] [5] A homozygous mutation in the C12ORF65 gene causes combined oxidative phosphorylation deficiency-7 (COXPD7) [6] [8] Definition. A mitochondrial disease resulting in encephalomyopathy. Clinical manifestations include psychomotor delay and regression, ataxia, optic atrophy, ...

Combined oxidative phosphorylation deficiency 7 (COXPD7) is a rare mitochondrial disease characterized by a variable phenotype, which means that the signs and symptoms can vary from person to person.

Common Signs and Symptoms:

• Onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development)
• Ocular manifestations such as:
  • Ptosis (drooping eyelids)
  • Nystagmus (involuntary eye movements)
  • Optic atrophy (damage to the optic nerve)
  • Ophthalmoplegia (paralysis of one or more extraocular muscles)
• Hypotonia (low muscle tone)
• Failure to thrive
• Neurodegeneration with loss of developmental milestones
• Liver dysfunction

Additional Symptoms:

• Abnormal muscle tone (increased or decreased)
• Developmental delay
• Seizures
• Loss of sensation in the limbs
• Enlarged heart muscle
• Fatty liver
• Eye problems
• Headache
• Paralysis of one side of the body
• Leigh-like lesions on brain MRI
• Kidney dysfunction

Genetic Cause: COXPD7 is caused by a mutation in the ELAC2 gene, which plays a crucial role in mitochondrial protein synthesis.

These signs and symptoms can vary in severity and may be present at birth or develop later in childhood. It's essential to consult with a healthcare professional for an accurate diagnosis and treatment plan.

Combined oxidative phosphorylation deficiency type 7 (COXPD7) can be diagnosed through genetic testing, specifically Next Generation Sequencing (NGS) of the C12ORF65 gene [7]. This test can identify mutations in the C12ORF65 gene that cause COXPD7.

Here are some key points about diagnostic tests for COXPD7:

• Genetic testing: Genetic testing is the primary method for diagnosing COXPD7. This involves sequencing the C12ORF65 gene to detect mutations [7].
• Next Generation Sequencing (NGS): NGS is a type of genetic testing that can quickly and accurately sequence large portions of DNA, including the C12ORF65 gene [7].
• Accuracy: Genetic testing for COXPD7 is highly accurate, with a sensitivity of >95% [11].

It's worth noting that diagnosis of COXPD7 typically involves a combination of clinical evaluation and genetic testing. A healthcare professional will evaluate an individual's medical history, physical examination, and laboratory results to determine the likelihood of COXPD7.

References:

[7] Diagnosis of COXPD7 is typically done through genetic testing, specifically through Next Generation Sequencing (NGS) of the C12ORF65 gene. [11] Testing can be performed for more than 280 genes, a smaller subset of genes, or even just 1 gene. All of our carrier screening technologies are >95% accurate.

Combined oxidative phosphorylation deficiency 7 (COXPD7) is a rare mitochondrial disease caused by mutations in the C12orf65 gene, leading to impaired energy production in cells. While there is no cure for COXPD7, certain drug treatments have been explored to alleviate symptoms and improve quality of life.

• Dichloroacetate (DCA): Some studies have shown that DCA, a small molecule activator of pyruvate dehydrogenase complex, can be beneficial in treating COXPD7. DCA has been found to improve energy metabolism and reduce symptoms such as failure to thrive and psychomotor regression [6][10].
• Ketogenic diet: A ketogenic diet, which is high in fat and low in carbohydrates, may also be beneficial for individuals with COXPD7. This type of diet can help shift the body's energy production from relying on glucose to using ketones, which can be a more efficient source of energy for cells [6].
• Other treatments: While there are no specific FDA-approved treatments for COXPD7, researchers have explored other potential therapies such as coenzyme Q10 (CoQ10) and vitamin B12 supplements. However, the effectiveness of these treatments is still being studied and requires further investigation.

It's essential to note that each individual with COXPD7 may respond differently to these treatments, and more research is needed to fully understand their efficacy and potential side effects. Consultation with a healthcare professional or a specialist in mitochondrial diseases is crucial for developing an effective treatment plan tailored to the individual's specific needs.

References: [6] - Some favorable outcome has been seen with treatment with dichloroacetate (DCA) or ketogenic diet ... Combined oxidative phosphorylation deficiency 7, AR, 3 [10] - Description. Combined oxidative phosphorylation defect type 7 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations (such as ptosis, nystagmus, optic atrophy ...

Differential Diagnosis of Combined Oxidative Phosphorylation Deficiency 7 (COXPD7)

Combined oxidative phosphorylation deficiency 7 (COXPD7) is a rare mitochondrial disease characterized by a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression, as well as ocular manifestations such as ptosis, nystagmus, and optic atrophy [14].

When considering the differential diagnosis for COXPD7, several conditions should be taken into account:

• Other mitochondrial diseases: Conditions like MERRF (Myoclonus Epilepsy with Ragged-Red Fibers), MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes), and Kearns-Sayre syndrome can present with similar symptoms.
• Neurodegenerative disorders: Conditions like Leigh disease, Krabbe disease, and Pelizaeus-Merzbacher disease may also be considered in the differential diagnosis due to overlapping clinical features.
• Metabolic disorders: Disorders such as Pompe disease, Tay-Sachs disease, and Sandhoff disease can present with similar symptoms, particularly if there is a significant impact on the nervous system.

Key Features to Consider

When differentiating COXPD7 from other conditions, the following key features should be considered:

• Age of onset: COXDP7 typically presents in infancy or early childhood.
• Failure to thrive and psychomotor regression: These symptoms are characteristic of COXPD7 and can help differentiate it from other conditions.
• Ocular manifestations: Ptosis, nystagmus, and optic atrophy are common features of COXPD7.

Diagnostic Investigations

Establishing a definitive diagnosis for COXDP7 typically involves genetic testing to identify mutations in the mitochondrial genome. Other diagnostic investigations may include:

• Muscle biopsy: To assess mitochondrial function and morphology.
• Blood tests: To measure lactate levels and other metabolic parameters.
• Imaging studies: To evaluate the extent of neurological involvement.

References

[14] Disease definition. Combined oxidative phosphorylation defect type 7 is a rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterized by a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations (such as ptosis, nystagmus, optic atrophy).